In attempt to make significant pharmacologically active molecule, we report here the synthesis and in vitro antimicrobial activity of various series of 3 – (4 – fluorophenyl) - 6 – substituted phenyl [1, 2, 4] triazolo [3, 4 – b] [1, 3, 4] thiadiazole derivatives was prepared by the reaction of carbon di sulfide, hydrazine hydrate. The compounds have been prepared by using P-toluene sulphonic acid, dimethyl formamide, 4-fluoro benzaldehyde, substituted benzaldehyde under conventional and microwave method. The products were found to be solid. The six compounds are characterized by analytical UV, IR, Mass, NMR. The compounds were screened for antitubercular activity against Mycobacterium tuberculosis species by using alamar blue assay method.